Li Shuangshuang, Du Yushi, Chen Guanyu, Mao Yihui, Zhang Wenyu, Kang Mengxi, Zhu Shasha, Wang Dongliang
Department of Nutrition, School of Public Health, Sun Yat-sen University, Northern Campus, Guangzhou 510080, China.
Guangdong Provincial Key Laboratory for Food, Nutrition and Health, Guangzhou 510080, China.
Nutrients. 2025 Mar 20;17(6):1090. doi: 10.3390/nu17061090.
: Non-resolving inflammation in macrophage-like cells (MLCs) transdifferentiated from vascular smooth muscle cells and monocyte-derived macrophages aggravates atherosclerosis. We previously showed that polyphenolic protocatechuic acid (PCA) could reduce inflammation burden in monocyte-derived macrophages; however, it remains unknown how this compound affects MLCs inflammation. : MLCs from the transdifferentiation of vascular smooth muscle cells induced by cholesterol and 30-week-old male ApoE mice fed a semi-purified AIN-93G diet containing either 0.003% (wt:wt) of PCA for a duration of 20 weeks were used to examine the impact of PCA on the inflammatory response of MLCs. Physiologically achievable doses of PCA (0.25-1 μM) dose-dependently inhibited lipopolysaccharide-induced NF-κB activation and simultaneously reduced pro-inflammatory cytokine levels. Mechanistically, this effect was mediated by effecting exportin-1 function, promoting nuclear export of phosphorylated-p65, independent of NF-κB kinase inhibitor α/β/γ, NF-κB inhibitor α, or importin-mediated nuclear import of -p65. PCA reduced the nucleocytoplasmic ratio of exportin-1 (44%) without altering its abundance. Importantly, dietary supplementation with PCA reduced interleukin-1β content within MLCs in atherosclerotic plaques of ApoE mice. In addition, dietary PCA reduced MLCs content in atherosclerotic plaques. : PCA could attenuate inflammatory response in MLCs by targeting exportin-1 and also could inhibit the transdifferentiation of vascular smooth muscle cells into MLCs within atherosclerotic plaques, which might promote the translation from preclinical studies to clinical trials in patients with atherosclerosis.
从血管平滑肌细胞和单核细胞衍生的巨噬细胞转分化而来的巨噬细胞样细胞（MLCs）中无法消退的炎症会加重动脉粥样硬化。我们之前表明，多酚原儿茶酸（PCA）可以减轻单核细胞衍生的巨噬细胞中的炎症负担；然而，这种化合物如何影响MLCs炎症仍不清楚。：使用由胆固醇诱导的血管平滑肌细胞转分化产生的MLCs以及30周龄雄性ApoE小鼠，这些小鼠喂食含有0.003%（重量：重量）PCA的半纯化AIN-93G饮食，持续20周，以检查PCA对MLCs炎症反应的影响。生理上可达到的PCA剂量（0.25 - 1μM）呈剂量依赖性地抑制脂多糖诱导的NF-κB活化，并同时降低促炎细胞因子水平。从机制上讲，这种作用是通过影响输出蛋白-1的功能介导的，促进磷酸化-p65的核输出，独立于NF-κB激酶抑制剂α/β/γ、NF-κB抑制剂α或输入蛋白介导的-p65的核输入。PCA降低了输出蛋白-1的核质比（44%），而不改变其丰度。重要的是，在ApoE小鼠动脉粥样硬化斑块中，饮食补充PCA降低了MLCs中的白细胞介素-1β含量。此外，饮食中的PCA降低了动脉粥样硬化斑块中的MLCs含量。：PCA可以通过靶向输出蛋白-1减轻MLCs中的炎症反应，并且还可以抑制动脉粥样硬化斑块内血管平滑肌细胞向MLCs的转分化，这可能会促进从动脉粥样硬化患者的临床前研究向临床试验的转化。
